Fibrinolytic activity after administration of diflunisal and aspirin: A double-blind, randomized, placebo-controlled clinical trial

A double-blind, randomized, placebo-controlled clinical trial was conducted to determine whether fibrinolysis was increased by the chronic administration of aspirin or diflunisal. Healthy male and female volunteers were randomized to receive either aspirin (1,300 mg every 12 h; 10 subjects), diflunisal (1,000 mg initially, then 500 mg every 12 h; 10 subjects), or placebo (10 subjects) for 8 days. Fibrinolytic activity was examined with the clot lysis assay, using native whole blood, platelet-rich plasma, and platelet-poor plasma, and with the kaolin-activated euglobulin lysis test. In addition, measurements were made of fibrinogen, fibrin/fibrinogen degradation products, plasminogen, and the thrombin time. Clot lysis was greater in whole blood and platelet-rich plasma than in platelet-poor plasma, and increased lysis was observed in specimens obtained in the afternoon as compared to those obtained in the morning. Fibrinolytic activity in the afternoon samples was significantly enhanced by both aspirin and diflunisal at the start of the trial (p < 0.05), but by the afternoon of day 8, only aspirin showed some enhancement. Fibrinolytic activity, as measured by the euglobulin lysis time, actually declined in all study groups during the course of drug administration. No significant changes were recorded in any of the other assayed hemostatic parameters. We conclude that aspirin and diflunisal exert a modest, nonsustained enhancing effect on fibrinolysis in normal subjects.